The role of acidosis and an acid-sensing ion channels subunit (ASIC1a) in epilepsy-induced spine remodeling

HE Jiang#， GONG Xiao-Qin#， LIU Dan， ZENG Yan*

(Brain and Cognition Research Institute， Wuhan University of Science and Technology， Wuhan 430065， China)

Abstract: It is well known that recurrent seizures induce spine loss， which may be critical for epileptogenesis， seizure termination， or long-term cognitive changes. However， the mechanisms that regulate spine remodeling in epilepsy remain not entirely clear. Researches have demonstrated that recurrent seizures generate acidosis， or a decrease in extracellular brain pH value. ASIC1a plays a particularly important role in acid-sensing in the brain. This article summarizes the recent progress related to this issue based on the work in our lab and others， elucidates the underlying molecular mechanisms. We suggest that acidosis has differential effects on network excitability at different stages during seizure progression. The effect of H+ on pyramidal neurons and interneurons is determined by both the amplitude and location of acidosis during epileptiform activity (EA). During seizure onset， H+ primarily activates pyramidal neurons and facilitates EA. At later stages， when acidosis becomes global， H+ activates inhibitory circuits and contributes to seizure termination. The future study should investigate the role of H+ in seizure progression with an emphasis on seizure-induced spine loss， which has potentially important implications in epileptogenesis and seizure progression as well as understanding chronic effects of epilepsy.